Unusual susceptibility to mycobacterial infections can be caused by deleterious mutations in genes that encode the interferon-γ receptor 1 chain. Such mutations hamper the activation of macrophages by a type 1 immune response and result in enhanced survival of intracellular pathogens. We here report two patients with unusual mycobacterial infections, both diagnosed with homozygous deleterious interferon-γ receptor 1 gene mutations. Patient 1 became ill after Bacillus Calmette-Guérin vaccination at the age of 9 months and died at the age of 18 months. She carried a homozygous C71Y mutation in the extracellular part of the mature interferon-γ receptor 1 protein, resulting in the lack of detectable protein expression and absence of interferon-γ dependent signaling. Patient 2 became ill at the age of 3 years, is still alive at 19 years of age, and has suffered from five successive infection episodes with atypical mycobacteria. A homozygous splice-site mutation in intron 3 was identified, resulting in the deletion of exon 3 at the mRNA level and consequently a truncated interferon-γ receptor 1 protein with absence of the transmembrane domain. Protein expression and interferon-γ dependent signaling were not detectable.

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Keywords Deleterious IFNGR1 mutations, ELISA, Flow cytometric analysis, Mycobacterial infection, Splice-site mutation
Persistent URL dx.doi.org/10.1007/s10875-007-9097-8, hdl.handle.net/1765/35908
Noordzij, J.G., Hartwig, N.G., Verreck, F.A.W., de Bruin-Versteeg, S., de Boer, T., Dissel, J.T.V., … van Dongen, J.J.M.. (2007). Two patients with complete defects in interferon gamma receptor-dependent signaling. Journal of Clinical Immunology, 27(5), 490–496. doi:10.1007/s10875-007-9097-8